Effect of digital ocular massage on intraocular pressure and Schlemm's canal dimensions.

Digital ocular massage has been reported to temporarily lower intraocular pressure (IOP). This could be related to an enhanced aqueous humor outflow; however, the mechanism is not clearly understood. Using anterior segment optical coherence tomography, the Schlemm's canal (SC) and trabecular meshwork (TM) can be imaged and measured. Here, 66 healthy adults underwent digital ocular massage for 10 min in their right eyes. The IOP and dimensions of the SC and TM were measured before and after ocular massage. All subjects demonstrated IOP reduction from 15.7 ± 2.5 mmHg at baseline to 9.6 ± 2.2 mmHg immediately after, and median of 11.6 mmHg 5-min after ocular massage (Friedman's test, p < 0.001). There was significant change in SC area (median 10,063.5 µm2 at baseline to median 10,151.0 µm2 after ocular massage, Wilcoxon test, p = 0.02), and TM thickness (median 149.8 µm at baseline to 144.6 ± 25.3 µm after ocular massage, Wilcoxon test, p = 0.036). One-third of the subjects demonstrated collapse of the SC area (-2 to -52%), while two-thirds showed expansion of the SC area (2 to 168%). There were no significant changes in SC diameter (270.4 ± 84.1 µm vs. 276.5 ± 68.7 µm, paired t-test, p = 0.499), and TM width (733.3 ± 110.1 µm vs. 733.5 ± 111.6 µm, paired t-test, p = 0.988). Eyes with a higher baseline IOP demonstrated a greater IOP reduction (Pearson correlation coefficient r = -0.521, p < 0.001). Eyes with smaller SC area at baseline showed greater SC area expansion (Pearson correlation coefficient = -0.389, p < 0.001). Greater IOP reduction appeared in eyes with greater SC area expansion (Pearson correlation coefficient r = -0.306, p = 0.01). Association between change in IOP and change in TM thickness was not significant (Spearman's ρ = 0.015, p = 0.902). Simple digital ocular massage is an effective method to lower IOP values, and change in the SC area was significantly associated with IOP changes.

Comparison of Schlemm's Canal Morphology Parameters Between Propensity Score-Matched Primary Open-Angle Glaucoma and Exfoliation Glaucoma.

Purpose: This study aimed to histologically compare the status of Schlemm's canal (SC) and Schlemm's canal endothelial (SCE) cells between trabeculectomy specimens from patients with primary open-angle glaucoma (POAG) and exfoliation glaucoma (EXG). Methods: A total of 182 eyes from 152 patients with POAG and 138 eyes from 116 patients with EXG underwent immunohistochemical staining for thrombomodulin. Equal numbers of cases were selected from both groups using propensity score matching. The following parameters were evaluated: total SC length, staining positive and negative SC length (PSC and NSC, respectively), opened and closed SC length, staining positive and opened SC length, staining positive and closed SC length, staining negative and opened SC length (NOSC), and staining negative and closed SC length. Results: After matching for age and gender, 87 cases were selected in each group. The EXG group had significantly higher preoperative IOP and medication scores. PSC was significantly longer in the POAG group, while NSC and NOSC were longer in the EXG group. Multiple regression analysis of these 174 cases revealed that PSC was significantly shorter in the EXG group. After matching for age, gender, preoperative IOP, and medication score, 64 cases were selected in each group, and NOSC was significantly longer in the EXG group. Conclusions: These findings suggest that in EXG, SCE loss occurs independently of background factors such as aging and medication use. The loss of SCE may have a more critical impact on IOP elevation in EXG compared to POAG.

Macrophage-induced integrin signaling promotes Schlemm's canal formation to prevent intraocular hypertension and glaucomatous optic neuropathy.

Schlemm's canal (SC) functions to maintain proper intraocular pressure (IOP) by draining aqueous humor and has emerged as a promising therapeutic target for glaucoma, the second-leading cause of irreversible blindness worldwide. However, our current understanding of the mechanisms governing SC development and functionality remains limited. Here, we show that vitronectin (VTN) produced by limbal macrophages promotes SC formation and prevents intraocular hypertension by activating integrin αvß3 signaling. Genetic inactivation of this signaling system inhibited the phosphorylation of AKT and FOXO1 and reduced ß-catenin activity and FOXC2 expression, thereby causing impaired Prox1 expression and deteriorated SC morphogenesis. This ultimately led to increased IOP and glaucomatous optic neuropathy. Intriguingly, we found that aged SC displayed downregulated integrin ß3 in association with dampened Prox1 expression. Conversely, FOXO1 inhibition rejuvenated the aged SC by inducing Prox1 expression and SC regrowth, highlighting a possible strategy by targeting VTN/integrin αvß3 signaling to improve SC functionality.

Assessment of Schlemm's canal with swept-source optical coherence tomography in Graves' ophthalmopathy.

PURPOSE: To evaluate the Schlemm's canal (SC) parameters obtained by swept-source optical coherence tomography (OCT) different in Graves' ophthalmopathy (GO) eyes compared to healthy eyes. METHODS: This cross-sectional observational study evaluated 64 eyes of 32 GO cases and 56 eyes of 28 healthy controls. The study was conducted between October 2020 and June 2021. SC images were obtained from the temporal limbus of individuals using swept-source OCT. SC length (SCL) and SC area (SCA) were measured. The relationship between SC parameters in the patient group and intraocular pressure (IOP), retinal nerve fiber layer (RNFL) thickness, Graves' disease (GD) duration, and clinical activity score (CAS) was evaluated. RESULTS: In the GO group, 64 eyes of 32 patients were evaluated, and in the age and gender-matched healthy control group, 56 eyes of 28 individuals were assessed. SC images from 4 eyes of 4 patients in the patient group and 1 eye of 1 patient in the control group were not clear, preventing SCL and SCA measurements for these eyes. SCL and SCA measurements were found to be lower, and IOP and Hertel values were higher in the GO group compared to the healthy controls. However, no significant correlation was observed between SCL and SCA with IOP, RNFL thickness, GD duration, GO duration, or CAS in the GO group. In the GO group, the mean value of SCA was found to be higher in eyes with glaucoma or OHT compared to those without. CONCLUSION: These findings indicate that SC in GO-affected eyes is shorter and has a smaller area than in healthy individuals. Additionally, higher IOP and Hertel values were observed in the GO group compared to healthy controls. This study suggests that assessing SC using anterior segment OCT could provide valuable insights into the regulation of IOP and the development of glaucoma in GO-affected eyes.

The effect of uneventful cataract surgery on Schlemm's canal and the trabecular meshwork in cases with pseudoexfoliation.

PURPOSE: To evaluate the effect of uneventful cataract surgery on Schlemm's canal (SC) and the trabecular meshwork (TM) in cases with pseudoexfoliation (PX). METHODS: In this prospective study, 37 PX and 37 normal eyes, who underwent cataract surgery, were included. The PX group was further divided into two subgroups: PX syndrome (PXS) and PX glaucoma (PXG). Preoperative complete ophthalmologic examination, anterior segment (AS) imaging using a Scheimpflug camera, and measurements of SC length and area and TM thickness and length using AS optical coherence tomography (AS-OCT) were performed in all cases. All measurements were repeated at the first and third months after surgery. RESULTS: Preoperative intraocular pressure (IOP), AS parameters, SC, and TM values showed no significant differences between the groups (p > 0.05). After surgery, there was a significant increase in AS parameter values and a significant decrease in IOP values in both the PX and control groups (p < 0.05). The nasal and temporal SC area showed a significant increase in the PX group after surgery (p = 0.007, p = 0.003, respectively). In the subgroup analysis, the only significant change in the nasal and temporal SC area was in the PXS group (p = 0.006, p = 0.003, respectively). CONCLUSION: Cataract surgery resulted in an increase in the SC area in patients with PXS. This increase may be due to multiple mechanisms including the IOP-lowering effect of cataract removal, change in AS, and removal of intraocular PX material after surgery.

Targeting YAP/TAZ mechanosignaling to ameliorate stiffness-induced Schlemm's canal cell pathobiology.

Pathological alterations in the biomechanical properties of the Schlemm's canal (SC) inner wall endothelium and its immediate vicinity are strongly associated with ocular hypertension in glaucoma due to decreased outflow facility. Specifically, the underlying trabecular meshwork is substantially stiffer in glaucomatous eyes compared with that from normal eyes. This raises the possibility of a critical involvement of mechanotransduction processes in driving SC cell dysfunction. Yes-associated protein (YAP) has emerged as a key contributor to glaucoma pathogenesis. However, the molecular underpinnings of SC cell mechanosignaling via YAP and transcriptional coactivator with PDZ-binding motif (TAZ) in response to glaucomatous extracellular matrix (ECM) stiffening are not well understood. Using a novel biopolymer hydrogel that facilitates dynamic and reversible stiffness tuning, we investigated how ECM stiffening modulates YAP/TAZ activity in primary human SC cells, and whether disruption of YAP/TAZ mechanosignaling attenuates SC cell pathobiology and increases ex vivo outflow facility. We demonstrated that ECM stiffening drives pathologic YAP/TAZ activation and cytoskeletal reorganization in SC cells, which was fully reversible by matrix softening in a distinct time-dependent manner. Furthermore, we showed that pharmacologic or genetic disruption of YAP/TAZ mechanosignaling abrogates stiffness-induced SC cell dysfunction involving altered cytoskeletal and ECM remodeling. Finally, we found that perfusion of the clinically used, small molecule YAP/TAZ inhibitor verteporfin (without light activation) increases ex vivo outflow facility in normal mouse eyes. Collectively, our data provide new evidence for a pathologic role of aberrant YAP/TAZ mechanosignaling in SC cell dysfunction and suggest that YAP/TAZ inhibition has therapeutic value for treating ocular hypertension in glaucoma.NEW & NOTEWORTHY Pathologically altered biomechanical properties of the Schlemm's canal (SC) inner wall microenvironment were recently validated as the cause for increased outflow resistance in ocular hypertensive glaucoma. However, the involvement of specific mechanotransduction pathways in these disease processes is largely unclear. Here, we demonstrate that Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) are central regulators of glaucoma-like SC cell dysfunction in response to extracellular matrix stiffening and that targeted disruption of YAP/TAZ mechanosignaling attenuates SC cell pathobiology and enhances outflow function.